Police on Tuesday detained 513 undocumented migrants from Latin America and Asia who were crammed into two trucks bound for the United States.
The migrants, from Latin America, Japan, China, India and Nepal, "were travelling in inhuman conditions" in southeastern Chiapas state, near the Guatemalan border, the local attorney general's office said in a statement.
Police stopped the trucks, carrying 240 and 273 people, on the outskirts of state capital Tuxtla Gutierrez on Tuesday, after they accelerated through a vehicle scanner at a police checkpoint, the statement said.
Officers chased down the vehicles shortly afterwards, it added.
"It is the largest rescue of migrants travelling in inhuman conditions," said a spokesman from the attorney general's office, declining to be named.
Police detained the Mexican drivers of the two trucks, and the migrants were provided with aid and food, the statement said.
Mexican lawmakers last month unanimously approved a law to "strengthen the protection and security" of migrants amid widespread abuse.
Rights groups have long criticised Mexico for failing to protect tens of thousands of migrants, mainly from Central America, who risk their lives trying to cross the vast country to illegally enter the United States each year.
The gruesome discovery of 72 murdered migrants from Central and South America in northeastern Tamaulipas state last August increased pressure on the government to act.
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